Pediatric renal cell carcinoma: clinical, pathologic, and molecular abnormalities associated with the members of the mit transcription factor family.

We describe the clinical features, outcome, pathology, cytogenetics, and molecular aspects of 13 pediatric papillary, renal cell carcinomas during a 19-year period. Seven cases (54%) had translocations involving Xp11.2 (TFE3). They were identified by cytogenetic, molecular, andlor immunohistochemical analyses. All Xp11.2+ translocations were TFE3+ by immunostaining. Cytogenetic andlor polymerase chain reaction analyses identified 3 cases with t(X17) and 1 case with t(1; 17), and all had additional translocations. Histologic features in common. in TFE3+ tumors also were present in some TFE3-tumors. One TFE3-tumor had complex cytogenetic abnormalities, 55XY, +2, del(3)(p14),+7,+8,+12,+13,+16,+17,+20[11], and 2 cases had normal karyotypes. None had t(6;11)/TFEB+ immunostaining. Five cases hadfocal, weak MITF tumor immunostaining. The key clinical findings were as follows: (1) The presence of an Xp11.2 (TFE3) translocation frequently is associated with advanced stage at initial examination. (2) All patients who underwent complete, partial nephrectomy with clear margins (adequate only for stage 1) and resection of metastases were alive and relapse-free at last follow-up. (3) The mean +/- SD event-free survival and overall survival rates at 5,ears were both 92% +/- 7.4%. (4) One patient with a TFE3+ and MITF+ tumor and 66-87, XXY, der(1)t(1;8)del(4)(q?) der(11)t(11;15)der17t(X; 17) abnormalities died 9 months after diagnosis.